MicroRNA-34c inversely couples the biological functions of the runt-related transcription factor RUNX2 and the tumor suppressor p53 in osteosarcoma

Osteosarcoma (OS) is a primary bone tumor that is most prevalent during adolescence. RUNX2, which stimulates differentiation and suppresses proliferation of osteoblasts, is deregulated in OS. Here, we define pathological roles of RUNX2 in the etiology of OS and mechanisms by which RUNX2 expression is stimulated. RUNX2 is often highly expressed in human OS biopsies and cell lines. Small interference RNA (siRNA)-mediated depletion of RUNX2 inhibits growth of U2OS OS cells. RUNX2 levels are inversely linked to loss of p53 (which predisposes to OS) in distinct OS cell lines and osteoblasts. RUNX2 protein levels decrease upon stabilization of p53 with the MDM2 inhibitor Nutlin-3. Elevated RUNX2 protein expression is post-transcriptionally regulated and directly linked to diminished expression of several validated RUNX2 targeting microRNAs (miRNAs) in human OS cells compared to mesenchymal progenitor cells. The p53-dependent miR-34c is the most significantly down-regulated RUNX2 targeting miRNA in OS. Exogenous supplementation of miR-34c markedly decreases RUNX2 protein levels, while 3UTR reporter assays establish RUNX2 as a direct target of miR-34c in OS cells. Importantly, Nutlin-3 mediated stabilization of p53 increases expression of miR-34c and decreases RUNX2. Thus, a novel RUNX2-p53-miR34 network controls cell growth of osseous cells and is compromised in OS.

RUNX3 functions as an oncogene in ovarian cancer

The Runt domain transcription factor, RUNX3, has been shown to be a tumor suppressor in a variety of cancers including gastric, colon and breast cancer. Interestingly, an oncogenic role for RUNX3 has also been suggested in basal cell carcinoma and head and neck cancer. Here, we explore the role of RUNX3 in ovarian cancer.

Invariant Information Local Sub-map Filter (IILSF) for Efficient Simultaneous Localisation and Mapping of Large Environments

This paper presents an Invariant Information Local Sub-map Filter (IILSF) as a technique for consistent Simultaneous Localisation and Mapping (SLAM) in a large environment. It harnesses the benefits of sub-map technique to improve the consistency and efficiency of Extended Kalman Filter (EKF) based SLAM. The IILSF makes use of invariant information obtained from estimated locations of features in independent sub-maps, instead of incorporating every observation directly into the global map. Then the global map is updated at regular intervals. Applying this technique to the EKF based SLAM algorithm: (a) reduces the computational complexity of maintaining the global map estimates and (b) simplifies transformation complexities and data association ambiguities usually experienced in fusing sub-maps together. Simulation results show that the method was able to accurately fuse local map observations to generate an efficient and consistent global map, in addition to significantly reducing computational cost and data association ambiguities.

Elucidation of the Burkholderia cenocepacia hopanoid biosynthesis pathway uncovers functions for conserved proteins in hopanoid-producing bacteria

Hopanoids are bacterial surrogates of eukaryotic membrane sterols and among earth's most abundant natural products. Their molecular fossils remain in sediments spanning more than a billion years. However, hopanoid metabolism and function are not fully understood. Burkholderia species are environmental opportunistic pathogens that produce hopanoids and also occupy diverse ecological niches. We investigated hopanoids biosynthesis in Burkholderia cenocepacia by deletion mutagenesis and structural characterization of the hopanoids produced by the mutants. The enzymes encoded by hpnH and hpnG were essential for production of all C35 extended hopanoids, including bacteriohopanetetrol (BHT), BHT glucosamine and BHT cyclitol ether. Deletion of hpnI resulted in BHT production, while ΔhpnJ produced only BHT glucosamine. Thus, HpnI is required for BHT glucosamine production while HpnJ is responsible for its conversion to the cyclitol ether. The ΔhpnH and ΔhpnG mutants could not grow under any stress condition tested, whereas ΔhpnI, ΔhpnJ and ΔhpnK displayed wild-type growth rates when exposed to detergent, but varying levels of sensitivity to low pH and polymyxin B. This study not only elucidates the biosynthetic pathway of hopanoids in B. cenocepacia, but also uncovers a biosynthetic role for the conserved proteins HpnI, HpnJ and HpnK in other hopanoid-producing bacteria.whereas ΔhpnI, ΔhpnJ and ΔhpnK displayed wild-type growth rates when exposed to detergent, but varying levels of sensitivity to low pH and polymyxin B. This study not only elucidates the biosynthetic pathway of hopanoids in B. cenocepacia, but also uncovers a biosynthetic role for the conserved proteins HpnI, HpnJ and HpnK in other hopanoid-producing bacteria.

Efficient predictive demand response using laguerre functions

Predictive Demand Response (DR) algorithms allow schedulable loads in power systems to be shifted to off-peak times. However, the size of the optimisation problems associated with predictive DR can grow very large and so efficient implementations of algorithms are desirable. In this paper Laguerre functions are used to significantly reduce the size of the optimisation needed to implement predictive DR, thus significantly increasing the efficiency of the implementation. © 2013 IEEE.

Solar phase functions of cometary nuclei

Relatively few measurements of the solar phase function of cometary nuclei exist, despite the importance of this parameter in determining accurate sizes and its use in modeling surface properties. We make use of robotic telescopes and servicemode observing to monitor cometary nuclei over months at a time, combining intensive observations at a single epoch with regular short light-curve segments to efficiently account for brightness changes due to both nucleus rotation and changing solar phase angle. We present our latest results on comets 8P/Tuttle, 14P/Wolf, 67P/Churyumov- Gerasimenko and 110P/Hartley 3.

Intermittent and Scale-Invariant Intensity Fluctuations in Hot Coronal Loops

ABSTRACT BODY: To resolve outstanding questions on heating of coronal loops, we study intensity fluctuations in inter-moss portions of active region core loops as observed with AIA/SDO. The 94Å fluctuations (Figure 1) have structure on timescales shorter than radiative and conductive cooling times. Each of several strong 94Å brightenings is followed after ~8 min by a broader peak in the cooler 335Å emission. This indicates that we see emission from the hot component of the 94Å contribution function. No hotter contributions appear, and we conclude that the 94Å intensity can be used as a proxy for energy injection into the loop plasma. The probability density function of the observed 94Å intensity has 'heavy tails' that approach zero more slowly than the tails of a normal distribution. Hence, large fluctuations dominate the behavior of the system. The resulting 'intermittence' is associated with power-law or exponential scaling of the related variables, and these in turn are associated with turbulent phenomena. The intensity plots in Figure 1 resemble multifractal time series, which are common to various forms of turbulent energy dissipation. In these systems a single fractal dimension is insufficient to describe the dynamics and instead there is a spectrum of fractal dimensions that quantify the self-similar properties. Figure 2 shows the multifractal spectrum from our data to be invariant over timescales from 24 s to 6.4 min. We compare these results to outputs from theoretical energy dissipation models based on MHD turbulence, and in some cases we find substantial agreement, in terms of intermittence, multifractality and scale invariance. Figure 1. Time traces of 94A intensity in the inter-moss portions of four AR core loops. Figure 2. Multifractal spectra showing timescale invariance. The four cases of Figure 1 are included.

A First Step Towards Cost Functions for Quantum-dot Cellular Automata Designs

Quantum-dot cellular automata (QCA) is potentially a very attractive alternative to CMOS for future digital designs. Circuit designs in QCA have been extensively studied. However, how to properly evaluate the QCA circuits has not been carefully considered. To date, metrics and area-delay cost functions directly mapped from CMOS technology have been used to compare QCA designs, which is inappropriate due to the differences between these two technologies. In this paper, several cost metrics specifically aimed at QCA circuits are studied. It is found that delay, the number of QCA logic gates, and the number and type of crossovers, are important metrics that should be considered when comparing QCA designs. A family of new cost functions for QCA circuits is proposed. As fundamental components in QCA computing arithmetic, QCA adders are reviewed and evaluated with the proposed cost functions. By taking the new cost metrics into account, previous best adders become unattractive and it has been shown that different optimization goals lead to different “best” adders.